The major objective of this project is to describe the cellular mechanisms by which hormones, neurotransmitters and paracrines interact to control hydrogen ion secretion by parietal cells in the gastric mucosa. The experimental models that will be utilized include acutely isolated gastric glands and enriched parietal cell preparations. Studies designed to develop a means of culturing homogeneous, functionally responsive parietal cells will also be initiated. All of these cellular preparations will be used to study receptor mechanisms, the roles of calcium and cyclic nucleotides in stimulus-secretion coupling, cAMP-dependent and independent protein kinase activities as well as to identify and characterize phosphorylated intermediates involved in the regulation of the acid secretory process. Biochemical responses will be measured in conjunction with previously established indices of acid secretory responsiveness including cellular respiration, aminopyrine uptake and morphological transformations. The characterization and correlation of both physiological and biochemical parameters will provide a basis for determining the sequence of events that occur following secretagogue-receptor interactions and ultimate activation of the parietal cell hydrogen ion "pump". Through the study of both individual parietal cell function and gastric glands, which are composed of several cell types including endocine-like cells, significant basic information will be obtained that may ultimately provide for more enlightened clinical evaluation and treatment of peptic ulcer disease.